A major focus of the specific research deals with regulation of dopamine systems in the CNS and their interrelationships with other neuroregulators with which dopamine is colocalized or which it may regulate, particularly neuropeptides. It has become clear that understanding the interaction process between these neuroregulator systems is relevant to the treatment, and perhaps of the pathogenesis, of severe mental disorders. We propose to investigate in a coordinated manner several aspects of the regulation of various components of the dopamine and neuropeptide systems. The aims include: -To elucidate the pre- and post-synaptic neurochemical significance of the coexistence of dopamine with other neuroregulators, particularly neurotensin and CCK, in discrete brain regions using in vivo dialysis and voltammetry. -To further develop and utilize the in situ transcription technique, developed in this laboratory, to study the regulation of dopamine- neuropeptide interactions including effects of dopamine on neuropeptide mRNA concentrations and structure. -To clone the dopamine D2 receptor and study its regulation using the in situ transcription technique in order to study changes in mechanisms involving that receptor that may be critical to severe mental disorders and their treatment. The application is based on findings and methods developed through past research through this research scientist award. Techniques utilized in the interdisciplinary research within the laboratory include in vivo neuropharmacology, mass spectrometry, analytical neurochemistry, biochemical neuroanatomy, peptide neurobiology, and molecular neurobiology. The Research Scientist Award will facilitate research and training functions related to research.